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Essential Equations for Anaesthesia
Key Clinical Concepts for the FRCA and EDA
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Essential Equations
for Anaesthesia
Key Clinical Concepts for the FRCA and EDA
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Authors
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Foreword and contents editor
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FFICM
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Statistical editor
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University Printing House, Cambridge CB2 8BS, United Kingdom
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www.cambridge.org
Information on this title: www.cambridge.org/9781107636606
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Edward T. Gilbert-Kawai and Marc D. Wittenberg
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This publication is in copyright. Subject to statutory exception
and to the provisions of relevant collective licensing agreements,
no reproduction of any part may take place without the written
permission of Cambridge University Press.
First published 2014
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Gilbert-Kawai, Edward T.
Essential equations for anaesthesia : key clinical concepts for the FRCA and EDA / authors, s.
Dr. Edward T. Gilbert-Kawai, MBChB, Central London School of Anaesthesia, UK, Dr. Marc D. Wittenberg,
MBChB, BSc (Hons), FRCA, Central London School of Anaesthesia, UK ; foreword and contents editor,
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Dr. Wynne Davies, MBBCh, DRCOG, DCH, FRCA, FFICM, University College London Hospitals NHS
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Foundation Trust, UK, statistical editor, Dr. Rebecca Gilbert, PhD, School of Social and Community
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pages cm
Includes index.
si
hi
I. Wittenberg, Marc D. II. Davies, Wynne (David Wynne Lloyd) III. Gilbert, Rebecca. IV. Title.
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RD82.3.G55 2014
617.90 6076dc23 2013045304
accurate or appropriate.
..............................................................................................................................................
Every effort has been made in preparing this book to provide accurate and up-to-date information which is
in accord with accepted standards and practice at the time of publication. Although case histories are drawn
from actual cases, every effort has been made to disguise the identities of the individuals involved.
Nevertheless, the authors, editors and publishers can make no warranties that the information contained
herein is totally free from error, not least because clinical standards are constantly changing through
research and regulation. The authors, editors and publishers therefore disclaim all liability for direct or
consequential damages resulting from the use of material contained in this book. Readers are strongly
advised to pay careful attention to information provided by the manufacturer of any drugs or equipment
that they plan to use.
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To those nearest and dearest to me, to Ma for her omniscient
advice, and above all to Grace for putting up with me.
Ned Gilbert-Kawai
To my parents for their unwavering love and support, to Eytan
and Noa for showing me what life is about, and most of all to
my rock, Dalya, without whom none of this would be possible.
G
Marc Wittenberg
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Contents
SECTION 1 PHYSICS
Part 1a Gases
1. Boyles law 1
2. Charles law 3
3. Gay-Lussacs law (third gas law) 5
4. Avogadros equation 7
5. Universal gas equation 9
6. Daltons law of partial pressures 11
7. Henrys law 13
8. Grahams law of diffusion 15
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viii Contents
Part 1c Electricity
1. Ohms law, voltage, current and resistance 28
2. Capacitance and capacitors 31
3. Inductance and inductors 33
4. Work and power 35
5. Transformers 37
6. Electrical charge 39
Part 1d Other
1. Doppler equation and effect 41
2. BeerLambert law 43
3. Relative humidity 45
4. Natural frequency 46
5. Wave equation and ultrasound 48
SECTION 2 PHARMACOLOGY
Part 2a Pharmacokinetics
1. Bioavailability 50
2. Volume of distribution 53
3. Clearance 55
4. Hepatic clearance 57
5. Concentration and elimination 59
6. Plasma concentration and compartment models 61
7. Loading dose and maintenance dose 63
8. Exponential function and rate constant 65
9. Half-life and context-sensitive half-life 68
10. Time constant 71
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Contents ix
Part 2b Pharmacodynamics
1. Drugreceptor dissociation constant and affinity 77
2. Therapeutic index 79
SECTION 3 PHYSIOLOGY
Part 3a Cardiovascular
1. Cardiac output and cardiac index 81
2. Stroke volume 83
3. Ventricular stroke work and index 85
4. Ejection fraction and fractional area change 87
5. Coronary perfusion pressure and coronary blood flow 89
6. Bazetts formula QT interval corrected 91
7. The Fick principle cardiac output measurement 92
8. The Fick equation oxygen uptake measurement 94
9. Mean arterial pressure 96
10. Venous return 98
11. Total blood volume 100
12. Systemic vascular resistance 102
13. Uterine blood flow 104
14. StewartHamilton equation 106
15. Oxygen delivery 108
16. Oxygen extraction ratio 110
17. Oxygen content equation 112
18. The dilution principle measurement
of fluid compartment volume 114
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x Contents
Part 3b Respiratory
1. Diffusing capacity 115
2. Compliance 117
3. Bohr equation 119
4. Alveolar ventilation equation 121
5. Alveolar gas equation 123
6. Helium dilution technique 125
7. Spirometry: forced expiration 127
8. Lung volumes and capacities 128
9. Respiratory quotient and respiratory exchange ratio 130
10. Shunt equation 132
11. Pulmonary vascular resistance 134
Part 3c Renal
1. Renal filtration fraction 136
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Contents xi
8. pKa 157
9. Acidbase compensation simplified 159
10. HendersonHasselbalch equation 161
Part 3e Neurological
1. Cerebral perfusion pressure and intracranial pressure 163
2. Intraocular pressure 165
SECTION 4 STATISTICS
Appendix
1. The International System of Units 194
2. Units of measurement 196
Index 197
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Foreword
Sitting examinations is a stressful time; answers are often all too apparent in the
coffee room chat following the exit from the examination hall. The way we
retrieve and process information has changed. The long evenings spent in the
library browsing the Index Medicus are fortunately long gone, and have been
replaced by much more instant online resources. The information revolution
continues, and as wireless technology becomes universal, so access to information
will become even more instant.
However, interpretation and emphasis is always going to need guidance.
Deriving and remembering equations is a daunting task, particularly when trying
to relate them to a clinical context; this book brings together many of the
mathematical concepts in anaesthesia into one place. It is an invaluable reference
guide to the equations used in anaesthesia today, with a brief explanation of units,
and examples of each equations relevance to clinical practice.
While the authors have attempted to include all equations relevant to post-
graduate anaesthetic exams, it is not a panacea for all formulae, but a concise
reference text for revision purposes. Succinct and clearly laid out, it enables
candidates to build on their academic knowledge, and provides a fresh insight
into the clinical applications of the mathematical concepts relevant to
anaesthesia.
Doctors Gilbert-Kawai and Wittenbergs Essential Equations for Anaesthesia
successfully complements other key medical texts as an equation reference guide
that will be indispensable to all trainees in anaesthesia, and a refresher for those of
us who took the examinations some time ago, before the advent of the infor-
mation technology revolution.
xiii
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Preface
One must divide ones time between politics and equations. Equations however are
much more important to me, for whilst politics concerns the present, our equations are
for eternity.
Albert Einstein (18791955)
As practising anaesthetic registrars, we are keenly aware of the challenges and
pressures faced by all trainees taking the anaesthetic examinations. Among the
seemingly insurmountable mountain of facts and figures that one is expected to
know relating to physiology, pharmacology, physics and statistics, knowledge of
equations and their derivation, use and application to anaesthetics is an absolute
prerequisite.
Unfortunately, while commonly regarded by candidates as a nightmare exam
question, this is often a favourite with examiners, particularly in the spoken viva
exams. Easy marks to win if one can demonstrate their knowledge through a
straightforward, clinically applied approach, or easy marks to lose if poorly
answered. Learned by rote, attempts to derive and link their application to clinical
practice can leave a candidate floundering a huge forfeiture in an exam where
every mark counts.
With this in mind, and having had to refer to nearly 20 books and multiple
websites while undertaking our own revision, none of them contained a compre-
hensive list of the multitude of different equations that we were required to know.
And thus it was, during a coffee break between theatre lists, that the idea of this
book was born: a simple, handy, reference guide to all the equations required for
the anaesthetics examination, with concise explanations and examples of their
direct relevance to clinical practice.
The book is broadly divided into the four subject areas of physics, physiology,
pharmacology and statistics. Each equation is explained, derived where necessary,
and a worked or clinically relevant example provided to demonstrate its use.
Units and relevant terms are given and, where required, clear, concise diagrams
have also been provided to simplify understanding. For general interest, the
historical background relating to an equations nomenclature has also been given
wherever possible. We expect readers to use it as a source of reference, and
enablement to relate the equations to clinical anaesthesia and intensive care
medicine.
xv
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xvi Preface
Our hope is that a clearer understanding of the topic will significantly diminish
the fear around this important aspect of the exam. Indeed, it is also hoped that
this book will be of use not only to those preparing for examinations, but also to
practising anaesthetists, as many of the equations in this book are directly
relevant to clinical practice.
Because thorough preparation for any examination cannot be dependent on
one text alone, this book is intended to complement, rather than supplant, other
reference works, and is not a replacement for robust knowledge. Nor is there any
substitute for hard work. Our intention is that using this book will smooth your
passage towards successful completion of the examinations and we wish you good
luck: if you are reading this, it means there is light at the end of the tunnel.
EG-K and MW
October 2013
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Acknowledgements
xvii
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Boyles law
PV = K
Or
1
V
P
(at a constant temperature)
P = pressure
V = volume
K = constant
Units
None.
Explanation
Boyles law (Robert Boyle, 1662) describes one of the characteristics of an ideal
gas. It states that if the temperature of the gas is held constant, then pressure and
volume are inversely proportional.
An ideal gas is a theoretical gas that obeys the universal gas equation (refer to
page 9).
1. You are asked to transfer a patient that requires 15 l/minute of oxygen and there
is one full E-cylinder of oxygen available. How long will this last?
Boyles law can be used to determine the amount of oxygen available from a
cylinder (V2), as follows:
1
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2 Section 1: Physics & Part 1a: Gases
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Charles law
V
=K
T
Or
V T
(at a constant pressure)
V = volume
T = temperature
K = constant
Units
None.
Explanation
1. Spirometry
During pulmonary function testing, a patient will exhale gas at body temperature
(37 C) into a spirometer at room temperature.
3
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4 Section 1: Physics & Part 1a: Gases
2. Heat loss
During anaesthesia, the air around the body is heated by convection. As this
happens, according to Charles law, the volume of the mass of gas increases and
therefore rises away from the patient.
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Gay-Lussacs law (third gas law)
P
=K
T
Or
P T (at constant volume)
P = pressure
T = temperature
K = constant
Units
None.
Explanation
Gay-Lussacs law (Joseph Louis Gay-Lussac, 1802), often described as the third gas law,
describes one of the characteristics of an ideal gas. It states that if the volume of a fixed
mass of a gas is held constant, then the pressure and temperature are proportional.
An ideal gas is a theoretical gas that obeys the universal gas equation (refer to
page 9).
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6 Section 1: Physics & Part 1a: Gases
This is important in the storage of nitrous oxide with its low Critical Tempera-
ture. At room temperature, it is stored in a cylinder as a liquid, with vapour on
top. As the temperature rises, the pressure exerted by the vapour, the Saturated
Vapour Pressure, also rises. If this exceeds the pressure capacity of the cylinder,
then it could explode, as the volume is constant.
For this reason, the filling ratio for nitrous oxide in the UK is 0.75, but in hotter
climates is 0.67.
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Avogadros equation
V
=K
n
V = volume of gas
n = amount of substance of the gas
K = a proportionality constant
Units
None.
Explanation
The equation states equal volumes of gases at the same temperature and pressure
contain the same number of molecules regardless of their chemical nature and
physical properties.
This number (Avogadros number) is 6 1023 and is described as 1 mole.
1 mole = quantity of a substance containing the same number of particles as
there are atoms in 12 g of carbon12 = 6 1023.
The mass of gases is different, but the concept of number of molecules, or
moles, enables comparison between them.
One mole of any gas at STP occupies 22.4 litres.
7
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8 Section 1: Physics & Part 1a: Gases
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Universal gas equation
PV = nRT
P = pressure
V = volume
n = the number of moles of the gas
R = the universal gas constant (8.31 J/K/mol)
T = temperature
Units
None.
Explanation
The universal (or ideal) gas equation describes the behaviour of an ideal gas. It is
a combination of Avogadros law (refer to page 7), Boyles law (refer to page 1)
and Charles law (refer to page 3).
The universal gas equation may be used to calculate the contents of an oxygen
cylinder.
Referring to the equation, in normal circumstances T is constant at room
temperature, V is constant as the cylinder has a fixed volume, and R is by
definition a constant. These terms therefore may be practically removed from
the equation, and so
Pn
The gauge pressure (P) can thus be used to measure the amount of oxygen
remaining in the cylinder (n).
9
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10 Section 1: Physics & Part 1a: Gases
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Daltons law of partial pressures
Units
Units of pressure.
Explanation
Daltons law (John Dalton, 1801) states that in a mixture of gases the total
pressure is always equal to the sum of the individual partial pressures of the
gases present. The pressure of each gas is determined by both the number of
molecules present and the total volume occupied, and is independent of the
presence of any other gases in a mixture.
1. Calculate the alveolar partial pressure of oxygen (PAO2) given the following
conditions:
FiO2 = 21%
Body temperature = 37 C
Atmospheric pressure = 100 KPa
PACO2 = 4 KPa
11
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12 Section 1: Physics & Part 1a: Gases
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Henrys law
At constant temperature, the mass of a gas that dissolves in a given type and volume
of liquid is directly proportional to the partial pressure of that gas in equilibrium with
that liquid.
Partial pressure = the pressure which the gas would have if it alone occupied the
volume of the container.
Units
None.
Explanation
Henrys law (William Henry, 1803) explains that when a liquid is placed into a
closed container, with time equilibrium will be reached between the vapour
pressure of the gas above the liquid and the liquid itself.
This is equivalent to stating that the solubility of a gas in a liquid is directly
proportional to the partial pressure of the gas above the liquid.
According to Henrys law, the partial pressure of the anaesthetic agent in the
blood is proportional to the partial pressure of the volatile in the alveoli. There-
fore, if the inspired concentration of volatile agent in the gas mixture is increased,
then the concentration in the blood will also increase.
At altitude, this is still the case, as Henrys law also dictates that the only factors
that affect the partial pressure of an agent in the blood are:
the saturated vapour pressure (SVP) of the specific volatile agent;
its concentration in the alveolus; and
the ambient temperature.
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14 Section 1: Physics & Part 1a: Gases
SVP is not affected by ambient pressure. Standard vaporizer settings do not need
to be altered at altitude, except the TEC 6 which is heated and pressurized.
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Grahams law of diffusion
1
Rate of diffusion = pffiffiffiffiffiffiffiffi
MW
MW = molecular weight.
Units
Explanation
The rate of diffusion of a gas is inversely proportional to the square root of its
molecular weight.
Therefore, the larger the molecule, the slower it diffuses across a membrane.
The equations may relate to diffusion or effusion, depending on the size of the
hole in the membrane relative to molecular size. Effusion occurs where individual
molecules flow through a hole without collisions with other molecules.
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16 Section 1: Physics & Part 1a: Gases
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Pressure and force
Force
Pressure =
Area
Or
Force = Pressure Area
Units
Explanation
1. Syringes
If we take two syringes of differing size, one 2 ml and the other 20 ml, and fill
them with liquid, it is harder to inject from the larger one when applying a
constant and equal force. This is because, as the equation states, pressure and area
are inversely proportional, thus as the area of the plunger increases, the pressure
generated will be less. This equates to more force required to generate the same
amount of pressure.
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18 Section 1: Physics & Part 1b: Pressure and flow
In clinical practice, this is utilized in finding the epidural space because using a
wide-bore syringe makes it easier to identify loss of resistance within the low-
pressure space. Conversely, unblocking an intravenous catheter is easier with a
small syringe as a greater pressure may be achieved.
Many breathing circuits contain an APL valve, the aim of which is to adjust and
limit the amount of pressure in the circuit during manual or spontaneous
ventilation. The valve contains a spring, which can be compressed by turning
it, and this in turn exerts a force (F) on diaphragm with an appropriate area (A)
within the valve. In order for the valve to open, a certain pressure (P) must be
generated, which can be calculated using the equation.
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HagenPoiseuille equation
(and laminar flow)
4
Pd
Q=
128l
Or
Pr 4
Q=
8l
Q = flow
P = pressure drop along the tube
d = diameter of the tube
r = radius of the tube
= viscosity of the fluid
l = length of the tube
/128 = proportionality constant if diameter is used in the calculation
/8 = proportionality constant if radius is used in the calculation
Units
Explanation
The HagenPoiseuille (Gotthilf Heinrich Ludwig Hagen & Jean Louis Marie
Poiseuille, 1840) equation is used to describe the characteristics of laminar flow
through a tube. The fluid moves steadily, and all the particles follow the same line
of flow in parallel layers (streamlines).
It demonstrates that as the pressure differential along the tube increases, so
does flow, and also that flow is inversely proportional to viscosity and length.
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20 Section 1: Physics & Part 1b: Pressure and flow
Perhaps most importantly, the equation states that as the diameter or radius of
the tube increases, flow increases by the fourth power. This means that if the
radius doubles, then flow will increase by 16 times.
The equation only applies to Newtonian fluids, which include water but not
blood. Those are where the viscosity of the fluid is constant regardless of the
accelerating forces in the streamlines.
1. Intravenous cannulas
The larger the cannula, the faster the flow, increasing by the fourth power of the
radius. This explains why wider-bore cannulas, of the same length, have much
higher flow rates.
For example, the stated flow rate through a blue 22G cannula is 31 ml/min and
1,000 ml crystalloid will take 32 minutes to infuse. Contrast this with an orange
14G cannula, which has a stated flow rate of 270 ml/min and through which
1,000 ml of crystalloid will take about 3.5 minutes to infuse.
Also, a longer cannula of the same gauge, for example that in a central venous
catheter, will have slower flow because length (l) and flow (Q) are inversely related.
For this reason, standard multi-lumen central venous catheters are inappropriate
for rapid infusion of fluids or blood products in the emergency situation.
As long as gas flow through an endotracheal tube is laminar, the larger the tube,
the less resistance there is to flow. This may be relevant when patients are
breathing spontaneously via an endotracheal tube because a narrower tube will
increase the work of breathing.
Anaesthetic breathing circuits are designed to maintain laminar flow as much as
possible, and reduce the work of breathing for spontaneously ventilating patients.
Connections are kept straight, if possible, as acute angles can cause turbulent flow.
Also, unnecessarily long circuits will reduce flow. (Refer to page 21.)
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Reynolds number (and turbulent flow)
vd
Re =
Re = Reynolds number
= density of the fluid
v = velocity of the fluid
d = diameter of the tube
= viscosity of the fluid
Units
Because the units of the equation cancel each other out, Reynolds number is
dimensionless, i.e. it has no units.
Units of density are usually kg/m3.
Explanation
Reynolds number (Osborne Reynolds, 1883) describes the factors that determine
the critical velocity when flow becomes turbulent rather than laminar. In this
instance, the HagenPoiseuille equation (refer to page 19) no longer applies.
Turbulent flow refers to a situation in which a fluid moves in a disorganized
fashion and begins to swirl, forming eddy currents. As flow is unpredictable, there
is no single equation that defines the rate of turbulent flow.
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22 Section 1: Physics & Part 1b: Pressure and flow
This equation tells us that turbulent flow occurs when fluids flow at high
velocity, through large diameter tubes and when fluids are relatively dense.
Density is much more important than viscosity when it comes to turbulent
flow. It is defined as the mass of substance occupying a unit volume, as opposed
to viscosity which is a measure of its resistance to gradual deformation by shear
or tensile stress.
Measurements have shown that when:
Reynolds number < 2,000, there is likely to be laminar flow;
Reynolds number 2,0004,000, there is likely to be transitional flow (laminar
and turbulent); and
Reynolds number > 4000, there is likely to be turbulent flow.
1. Why is helium used in the management of upper airway obstruction and croup?
In large airways such as the larynx, trachea and large bronchi, flow is generally
turbulent because of their large diameter.
Reynolds number dictates that flow in this situation is, among other things,
dependent on the density of the gas. In these situations, Heliox (a mixture of 21%
oxygen and 79% helium) can be used as it has a significantly lower density than
air (0.5 g/l vs. 1.25 g/l at STP). The lower density decreases the Reynolds number,
such that there is a higher tendency for flow in the airways to become laminar,
thereby decreasing the work of breathing.
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Equation 1b.3: Reynolds number and turbulent flow 23
In the smaller airways, flow is more likely to be laminar and so Heliox is likely
to have a limited effect because laminar flow does not depend on the density of
the fluid.
However, caution should be taken using Heliox, as the patient could still be
rendered hypoxic due to the low oxygen concentration.
This concept also explains why helium-filled balloons rise, and why inhaling
helium will cause your voice to become high-pitched because the flow of gas
through the vocal cords is significantly greater!
Blood flow through vessels is usually laminar. However, when there is a disrup-
tion of flow such as a sharp bend or narrowing, then eddies and currents will
form causing turbulent flow.
In the case of carotid atheromas, as blood flows past the plaque, it becomes
turbulent and it is this which is audible with a stethoscope as a bruit.
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Laplaces law and tension
PR
T=
2t
Or simplified
T
For a cylinder : P =
R
2T
For a sphere with one liquid surface : P =
R
4T
For a bubble with two liquid surfaces : P =
R
P = pressure gradient
T = tension
t = wall thickness
R = radius
Units
None.
Explanation
24
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Equation 1b.4: Laplaces law and tension 25
Laplaces cylinder law explains that as the radius of the aorta increases, the
tension across its wall also increases so as to maintain the pressure gradient. As
tension increases, the risk of rupture increases, and thus abdominal aneurysms
larger than 5 cm require urgent repair.
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Bernoulli equation and Venturi effect
1 2
P+ v + gh = constant
2
P = pressure
= density
v = velocity of fluid
g = acceleration due to gravity
h = height of the tube
Units
Units of each term are varied, but as they refer to a constant they are not
important in describing the equation.
Explanation
For an ideal fluid, i.e. (i) non-compressible, (ii) non-viscousand (iii) flowing in a
laminar fashion, the sum of the pressure (p), kinetic 12 v2 and potential (gh)
energies per unit volume remains constant at all points.
Put simply, in order to abide by the law of conservation of energy, the total
energy within a fluid system must always remain constant. Therefore, if the
kinetic energy (velocity) of the fluid increases, then the potential energy (pres-
sure) will simultaneously fall.
In practical terms, the acceleration of fluid due to gravity can be discounted as
we are referring to a horizontal tube. Furthermore, the density of fluid will remain
the same, as will the height of the tube.
Thus, the equation can be simplified to:
1 2
P+ v = constant
2
Therefore, the Bernoulli principle (Daniel Bernoulli, 1738) states that if there is
an increase in the velocity of an ideal fluid, then there will be a proportional
decrease in its pressure.
26
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Equation 1b.5: Bernoulli equation and Venturi effect 27
The nozzle can have a fixed or variable aperture that is used to set the concen-
tration of oxygen that is delivered.
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Ohms law, voltage, current and resistance
V = IR
Units
Explanation
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Equation 1c.1: Ohms law, voltage, current and resistance 29
In order to calculate the total resistance within a circuit, the equations are as
follows:
Series : RT = R1 + R2 + R3 +
Parallel : 1/RT = 1/R1 + 1/R2 + 1/R3 +
where
RT = total resistance
Rn = each resistor in turn up to the total number.
Current describes moving charge, or flow of electrons, and Ohms law can be
thought of as analogous to water flow from a large container through a pipe out
of the side of the container that has a constriction within it: V is the height of the
water above where the pipe exits the container, I is the speed of the water out of
the pipe and R represents the constriction within the pipe. It is easy to see how, if
the height of the water increases, then current will increase; and if the constriction
in the pipe increases, then the current will decrease.
Therefore, I is proportional to V, and inversely proportional to R.
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30 Section 1: Physics & Part 1c: Electricity
Battery
R3 R4
G C
A
R1 R2
(Strain gauge)
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Capacitance and capacitors
C
F=
V
Or
1 2
E= CV
2
Units
As above.
Explanation
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32 Section 1: Physics & Part 1c: Electricity
Capacitance can exist between everyday objects that act as two metal plates. This
includes ECG leads, the patient, the operating table and theatre lights. Air is the
non-conducting substance, otherwise known as the dielectric. When two objects
act as a capacitor, this is called capacitative coupling, and can result in electro-
static interference.
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Inductance and inductors
Wb
H=
A
Units
As above.
Explanation
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34 Section 1: Physics & Part 1c: Electricity
Time (t )
Time (t )
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Work and power
Work done: W = F D
W = work done
F = force
D = distance
Units
Explanation
Work refers to the process by which a force acts on a body to move it in the
direction of the force. Energy is thereby expended. The unit, joule, refers to the
fact that it measure the amount of work done when a force of 1 newton (N)
moves its point of application 1 metre (m) in the direction of that force.
Power refers to the rate of work done, and is defined as the amount of energy,
in joules, consumed per unit time. Watts, named after James Watt (17361819),
is the unit of power. 1 Watt equals 1 Joule per second.
When referring to electrical power, the equation is as follows:
P=IV
where P = power, I = current and V = potential difference (voltage).
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36 Section 1: Physics & Part 1c: Electricity
The volume of gas (V) delivered is also a product of the distance moved (D)
and the area (A) of the bellows. As we know that force, F, is a product of pressure
(P) and area (A), these concepts can be combined to deduce that the work done
(W) by the ventilator is also a product of the volume of gas moved, and the
pressure required, as follows:
W=FD
and F=PA
and V=DA
So D = V/A
Therefore W = PA V/A = PV
The notion of electrical power can also be applied to the heart in that the power of
the heart is a product of the pressure (or potential) difference and the fluid flow
(or current).
The pressure difference in the left side is analogous to difference between the
mean arterial pressure and pulmonary venous pressure (which is normally 0),
and the current can be compared to the cardiac output. Similarly, for the right
side of the heart, the pressure difference would equate to mean pulmonary artery
pressure minus the right atrial pressure.
Therefore, the power of the heart may be calculated as pressure difference
cardiac output.
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Transformers
n1
V2 = V1
n2
Units
Voltage.
Explanation
A transformer is a static electrical device that transfers electrical energy from one
circuit to another by inductive coupling. Transformers are used to raise or lower
the voltage in a circuit depending on the requirements. An example is the
National Grid, where energy is transferred around the country by voltage rather
than current in order to reduce heat losses.
In its simplest form, a transformer consists of two lengths of insulated wire,
each wound (or coiled up) around an iron core. These coils tend to differ in terms
of the number of windings each has. An alternating current in the primary
winding creates a varying magnetic flux in the primary transformers core,
subsequently producing a magnetic flux and alternating current in the secondary
core and coil, respectively.
In an ideal transformer, i.e. a perfectly coupled one in which there is no loss of
energy, the voltage induced in the secondary coil may be calculated from the
above formula.
Importantly, the ratio of the electrical current strength, or amperage, in the two
coils is inversely proportionate to the ratio of the voltages, and thus the electrical
power (voltage multiplied by amperage) is the same in both coils.
37
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38 Section 1: Physics & Part 1c: Electricity
A transformer consists of two metal cores (termed primary and secondary), each
with an insulated wire coiled around it. The ratio of the number of turns in the
primary coil to the number of turns in the secondary coil, known as the turns
ratio, determines the ratio of the voltages in the two coils. For example, in a step-
up transformer there may be one turn in the primary coil, and 20 turns in the
secondary coil, such that the voltage in the secondary coil will be 20 times that in
the primary. Alternatively a step-down transformer will have more turns of wire
around the primary core as compared to the secondary core. The voltage induced
in one coil may be calculated if the number of coils in each core is known, as well
as the initial voltage.
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Electrical charge
Q = IT
Or
Q = CV
Q = charge
I = current
T = time (seconds)
C = capacitance
V = potential difference or voltage
Units
Coulomb.
Explanation
39
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40 Section 1: Physics & Part 1c: Electricity
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Doppler equation and effect
cf d
v=
2f T cos
v = flow velocity
c = the speed of sound in tissues
fd = Doppler frequency shift that is received
cos = cosine of the angle between the sound beam and moving fluid (45o)
fT = frequency of the transmitted ultrasound from the transducer (Hz)
Units
m/s.
Explanation
The Doppler effect is used in the measurement of the velocity of blood cells using
the oesophageal Doppler probe (ODP). The cardiac output and other variables
are then calculated.
The ultrasound probe contains a transmitter, which transmits ultrasonic waves
at frequency fT, and a receiving transducer, that detects the frequency of the
reflected ultrasound waves, fd.
41
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42 Section 1: Physics & Part 1d: Other
If red blood cells are moving towards or away from the transducer (like the
ambulance siren), then there is Doppler shift. The magnitude of this shift is
directly proportional to the velocity (v) of the blood cells.
Note that the cosine of 90 = 0. Therefore, if the probe is perpendicular to the
flow of blood, then there will be no Doppler shift. Therefore, the transducer of the
ODP is positioned at 45 to the flow of blood in order to assess its velocity.
Ideally, a Doppler shift should be parallel to the object being measured for
velocity for maximum accuracy; however, the 45 probe on the ODP is a
compromise.
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BeerLambert law
A = dc
A = absorbance
= molar extinction coefficient
d = path length in cm
c = molar concentration
Units
Variable.
Explanation
Combining the two laws means that the transmission of light through a
substance (the inverse of absorbance) is inversely proportional to its molar
concentration and thickness.
43
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44 Section 1: Physics & Part 1d: Other
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Relative humidity
e
= 100
e
= relative humidity
e = partial pressure of water vapour = absolute vapour pressure
e = saturated vapour pressure of water at a given temperature
Units
Percentage.
Explanation
Humidity, the mass of water vapour in the air, may be expressed in absolute,
relative or specific terms. Absolute humidity is the mass of water vapour per unit
volume of air. Specific humidity is the ratio of water vapour to dry air in a set
volume. Relative humidity is defined as the ratio of the partial pressure of water
vapour in the air at a given time (absolute vapour pressure) to the saturated
vapour pressure of water at the present temperature.
45
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Natural frequency
D
NF pffiffiffiffiffiffiffiffi
LCd
NF = natural frequency
D = catheter diameter
L = tube length
C = system compliance
d = fluid density
Units
Hertz (Hz).
Explanation
Every material has a frequency at which it freely oscillates, known as the natural
frequency. If a force with a similar frequency to the natural frequency is applied
to the system, it will begin to oscillate at its maximum amplitude. This is known
as resonance.
The system set-up for IABP monitoring consists of fluid-filled tubing, which is
attached to a bag of pressurized fluid at one end, and an intra-arterial catheter at
the other end. This tubing has a natural frequency at which it oscillates.
The arterial waveform is transmitted from the cannula in the artery to the
pressure transduced by means of a waveform which is made up of a number of
component sine waves. Should the natural frequency of the IABP system lie close
46
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Equation 1d.4: Natural frequency 47
to the frequency of any of the sine waves within the arterial waveform, then the
system will resonate, causing a distortion of the measurement. Therefore, to avoid
resonance at the high heart rates, the frequency response of the monitoring
system should exceed 30 Hz.
As can be seen by the equation, the natural frequency of the system is
increased by:
increasing the diameter of the tubing;
decreasing the tube length;
reducing the compliance of the tubing; and
reducing the density of the fluid within the tubing.
Ideally, therefore, arterial cannulae should be short, stiff and wide-bore, but not
so wide that they cause distal arterial occlusion. Similarly, the tubing that
connects the arterial cannula to the transducer should also be short, stiff and
wide-bore; however, for convenience, this is often quite long, although fairly stiff
and non-compliant.
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Wave equation and ultrasound
v =f
v = velocity
= wavelength
f = frequency
Units
m/s.
Explanation
For a sinusoidal wave, the mathematical relationship between the speed (v) of a
wave and its wavelength () and frequency (f) is derived by the equation above.
Wavelength and frequency can thus be calculated by rearranging the equation.
Assuming the sinusoidal wave is propagated at a constant velocity, wavelength is
inversely proportional to frequency, such that waves with lower frequencies have
longer wavelengths and vice versa.
1. Why are frequency and wavelength important for generating clear ultrasound
pictures?
Medical ultrasound uses sound waves with a frequency outside the audible limit
of normal human hearing. These are typically above 20,000 Hz, but may rise to
50 MHz.
While ultrasound cannot detect objects that are smaller than its wavelength
(and therefore higher frequencies of ultrasound produce better resolution), at a
given velocity the choice of frequency is a trade-off between imaging depth and
the quality of the image, as higher frequencies are more readily absorbed and
therefore do not penetrate as deep into the tissue. As v = f and v 1,540 m/s
48
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Equation 1d.5: Wave equation and ultrasound 49
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Bioavailability
AUC po xDoseiv
F=
AUC iv xDosepo
F = fraction absorbed
AUCpo = area under the curve oral route
AUCiv = area under the curve intravenous route
Doseiv = dose administered intravenous route
Dosepo = dose administered oral route
Units
Explanation
50
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Equation 2a.1: Bioavailability 51
Concentration (mg.ml1)
iv
Oral
Time (min)
1. Given the following, calculate the bioavailability of the oral dose of this antibiotic.
Dosepo 10 mg
Doseiv 10 mg
AUCpo 4.5 mg/ml/h
AUCiv 11.2 mg/ml/h
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52 Section 2: Pharmacology & Part 2a: Pharmacokinetics
Physiological factors:
gastric pH,
gastric emptying intestinal motility,
perfusion of gastrointestinal tract, first pass metabolism.
Pathological factors:
cardiac and liver disease,
enzyme inducers or inhibitors such as cytochrome P450,
vomiting,
diarrhoea.
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Volume of distribution
X
Vd =
C0
Vd = volume of distribution
X = amount of drug in the body (mg)
C0 = plasma concentration at time zero (mg/l)
Units
Litres.
Explanation
The volume of distribution (Vd) describes the apparent volume into which a drug
disperses in order to produce the observed plasma concentration (C0). In a one-
compartment model, Vd is the proportionality constant that relates the amount
of drug in the body to plasma concentration at time zero.
Vd is a theoretical volume that has no direct physiological meaning, and in
many cases it can be much larger than total body water. It does not correspond to
any particular physiological volumes. It is more a reflection of how a drug
distributes within the body in relation to its physicochemical properties such as
solubility, charge and molecular weight.
Propofol has a very large volume of distribution (up to 60 l/kg). This means that
the drug is more dilute than if solely distributed in the plasma alone, and thus it
must also be distributed within the tissues. As propofol is extremely lipid-soluble
(non-polar) a large proportion is taken up into fatty tissue. Drugs with high Vd also
include those that have low rates of ionization, or low plasma-binding capabilities.
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54 Section 2: Pharmacology & Part 2a: Pharmacokinetics
2. Calculate the Vd for the following theoretical anaesthetic drug given to a patient
weighing 60 kg.
X
Vd =
C0
= 1,000/2 = 500 litres
= 8.33 l/kg
It is likely from this that the drug is highly lipid-soluble as it has a very high Vd.
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Clearance
Cl = k V d
Or
Vd
Cl =
Cl = clearance
k = rate constant (for elimination)
Vd = volume of distribution
= time constant
Units
ml/min.
Explanation
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56 Section 2: Pharmacology & Part 2a: Pharmacokinetics
In practical terms, for most drugs, clearance is almost synonymous with renal
clearance even though other organs are involved in clearance. If a drug is cleared
by more than pathway, that clearance can be calculated for each pathway for
example, renal and hepatic and then added together to calculate the total
clearance.
1. Calculate the clearance for drug X that demonstrates first-order kinetics, given
the Vd = 10 litres, and k = 0.5/min.
The rate constant describes the proportion of plasma from which the drug is
removed per minute, in this case 50%. Clearance is the product of rate constant
and volume of distribution. Therefore:
2. Give examples of drugs that are 100% renally cleared and explain the implica-
tions of renal impairment.
(i) Lithium: this drug has a narrow therapeutic window. Therefore, in renal
impairment, estimates of renal function can be useful in determining if
low or high concentrations are due to poor compliance or under- or over-
dosing.
(ii) Allopurinol: estimates of renal function can be used to guide dosing as
well as clinical and biochemical measures of effect, such as serum urate
concentration.
(iii) Amoxicillin: this drug has a wide therapeutic window and therefore dosing
is not normally adjusted for short-term use in patients with renal disease.
However, estimates of renal clearance can be useful to identify those patients
who may need smaller doses or longer dose intervals.
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Hepatic clearance
CLH = Q ER
where
Ca Cv
ER =
Ca
Units
ml/min.
Explanation
Hepatic clearance (CLH) quantifies the loss of drug during its passage through the
liver. It is the product of hepatic blood flow multiplied by the extraction ratio (ER).
The extraction ratio is a measure of the organs relative efficiency in eliminat-
ing the drug from the systemic circulation during a single pass through the liver.
It can be determined by measuring the concentration of drug entering (Ca) and
leaving (Cv) the liver as shown by the equation above.
If the concentration leaving an organ is 0, then the drug has been totally
removed from the circulation, and consequently the ER = 1. Conversely, if the
concentration in Ca is the same as that in Cv then the ER = 0.
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58 Section 2: Pharmacology & Part 2a: Pharmacokinetics
1. How does the variation in blood flow to the liver affect clearance?
For drugs with a low extraction ratio (< 0.3) such as warfarin, diazepam and
theophylline, the venous drug concentration is virtually identical to the arterial
concentration and therefore the liver is poorly influenced by blood flow
variations.
For drugs with a high extraction ratio (> 0.7) such as lignocaine, verapamil and
propranolol, an increase in blood flow will increase the amount of drug presented
to the metabolizing enzymes, and so clearance will increase accordingly.
Hepatic clearance is influenced by blood flow entering the organ, and the
extraction ratio occurring within the organ. Any condition that affects either of
these will alter clearance.
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Concentration and elimination
C = C 0 e kt
C = concentration
C0 = concentration at time zero
t = time
k = rate constant
e = Eulers number (base to the natural logarithm = 2.718)
Units
mg/l or g/ml.
Explanation
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60 Section 2: Pharmacology & Part 2a: Pharmacokinetics
The rate constant defines the steepness of the wash-out curve. If all else were to
remain constant, and the rate constant doubled, the time for plasma concen-
tration to reach a given value would half. Conversely, if the rate constant is
halved, then the time to reach a given plasma concentration would double.
Propofol.
Fentanyl.
Thiopentone.
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Plasma concentration and compartment
models
One-compartment : C = Ae t
Two-compartment model : C = Ae t + Be t
Three-compartment model : C = Ae t + Be t + Ge t
C = plasma concentration
e = Eulers number
A = constant A
B = constant B
G = constant G
t = rate constant
t = rate constant
t = rate constant
Units
Explanation
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62 Section 2: Pharmacology & Part 2a: Pharmacokinetics
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Loading dose and maintenance dose
LD = loading dose
Vd = initial volume of distribution
Cp = required peak plasma concentration
Ratein = rate at which drug is administered
Cl = clearance
Units
Explanation
Patients are often given drugs by intravenous infusion. A loading dose is given in
order to attain a desired drug concentration rapidly, as opposed to waiting for a
longer period of time from a constant rate intravenous infusion reaching a
steady-state level. It is estimated by multiplying the concentration required
(Cp), by the volume of distribution (Vd). In practice, this is estimated using the
patients parameters such as gender, weight and height.
Once a steady state has been achieved, we can maintain its level if drug input
equals drug output. In this case, the frequency at which maintenance doses are
administered is dependent on the rate at which the drug is removed from the
plasma.
As we know that the rate of output is equal to elimination, which in turn is
equal to clearance multiplied by plasma concentration, we can say that to keep
plasma levels stable at a steady state:
Ratein = Cl C p
63
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64 Section 2: Pharmacology & Part 2a: Pharmacokinetics
Once the steady state has been reached, sometimes a bolus dose can be given if a
higher concentration is rapidly required during the infusion. The dose can be
calculated as follows:
Bolus dose = (C new C actual ) V p
1. A patient in the intensive care unit requires theophylline to treat their severe
asthma. Calculate the loading dose required.
2. Give examples of other drugs in the critical environment that make use of the
equations above.
Digoxin.
Vancomycin.
Phenytoin.
Propofol.
Remifentanil.
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Exponential function and rate constant
dC
C
dt
Or
dC
= kC
dt
dC = change in concentration
dt = change in time
C = concentration
k = constant of proportionality
Units
None.
Explanation
65
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66 Section 2: Pharmacology & Part 2a: Pharmacokinetics
1. Describe the shape of a negative exponential curve, and describe why it takes
that shape.
Time (t )
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Equation 2a.8: Exponential function and rate constant 67
2. An antiepileptic drug used to control seizures has a half-life of 8 hours. The drug
is effective if the patient has more than 25 mg of medicine in his body. If a
person takes an initial dose of 175 mg of medicine, will the medicine still be
effective 24 hours later?
m(t) = mo (0.5)t
so
m(3) = 175(0.5)3
m(3) = 21.88 mg
Therefore, the medicine is no longer effective after 24 hours.
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Half-life and context-sensitive half-life
t 1/2 = 0.693/k
Or
t 1/2 = (0.693Vd)/Cl
t1/2 = half-life
0.693 = ln(2) or loge(2)
Vd = volume of distribution
Cl = clearance
k = elimination rate constant
Units
Time = minutes.
Explanation
Half-life is the time taken for the plasma concentration of a drug to fall to 50% of
its initial value. It governs both the time to eliminate a single dose of a drug, and
the time taken for a drug to accumulate to a steady-state level during a constant
rate infusion or multiple dosing regimes. This is approximately five half-lives and
is normally determined experimentally.
Context-sensitive half-time (CSHT) is defined as the time taken for blood
plasma concentration of a drug to fall by 50%, after an infusion designed to
maintain a steady state, has been stopped. The CSHT is equal to the elimination
half-life, where context refers to the duration of the infusion.
68
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Equation 2a.9: Half-life and context-sensitive half-life 69
100
Percentage of initial
value (y)
50
25
t 1/2 t 1/2
Time (t)
Half-life depends on the elimination rate constant (k), which is the rate at
which the drug is removed from the body, and therefore may also be expressed
using clearance (Cl) and volume of distribution (Vd) (refer to page 53).
Additionally, half-life is related to the time constant () by a constant of
proportionality, where ln(2) equals 0.693 (refer to page 71).
t1/2 = 0.693
From this equation, we can clearly see that the half-life is shorter than the time
constant.
The half-life is the time taken for plasma concentration to fall to 50% of its initial
value. The volume of plasma remaining will diminish in the following manner:
1 half-life = 50% remaining
2 half-lives = 25% remaining
3 half-lives = 12.5% remaining
4 half-lives = 6.25% remaining
5 half-lives = 3.125% remaining
After 5 half-lives approximately 97% of the drug will have been eliminated. This
equates to approximately 3 time constants.
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70 Section 2: Pharmacology & Part 2a: Pharmacokinetics
Short
Adenosine (< 10 s).
Norepinephrine (2 min).
Intermediate
Salbutamol (23 h).
Morphine (23 h).
Long
Diazepam (20100 h).
Digoxin (2436 h).
Amiodarone (58 days).
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Time constant
= 1/k
Or
= V d /Cl
= time constant
k = rate constant
Vd = volume of distribution
Cl = clearance
Units
Time = minutes.
Explanation
71
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72 Section 2: Pharmacology & Part 2a: Pharmacokinetics
100
Percentage of initial
value (y)
50
37
Time (t )
The time constant may also be calculated from its relationship to clearance (Cl)
and volume of distribution (Vd).
Vd
=
Cl
1. Describe the difference between the half-life and time constant of a drug.
Time constant is defined as the time it would have taken the plasma concen-
tration to fall to zero if the original rate of elimination had continued.
Half-life is the time taken for the plasma concentration of a drug to fall to 50%
of its initial value.
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Rates of reaction
dA *
Zero order : = k
dt
dA
First order : = kA
dt
Units
Explanation
The rate of reaction describes the speed at which a process ensues. It may be
described as zero order or first order. It is commonly referred to when discussing
the elimination of drugs from the body.
73
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74 Section 2: Pharmacology & Part 2a: Pharmacokinetics
1. Give examples of zero-order and first-order kinetics, and briefly describe their
pharmacokinetics.
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MichaelisMenten equation
V max [s]
V=
K m + [s]
V = velocity of reaction (i.e. the rate at which an enzyme can metabolize its
substrate)
Vmax = maximum velocity of reaction
[s] = substrate concentration
Km = substrate concentration at which the velocity of the reaction (V) is half
maximal velocity (Michaelis constant)
Units
Explanation
75
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76 Section 2: Pharmacology & Part 2a: Pharmacokinetics
In simple terms,
V max [s]
V=
Km
In this instance, as the rate and substrate concentrations are directly proportional
to each other, the reaction is first-order kinetics (refer to page 73).
(2) When [s] Km, Km can be discounted, [s] consequently cancels out, thus:
V = V max
In this instance, as the rate is equal to the maximum velocity and independent
of the substrate concentration, the reaction is zero-order kinetics (refer to
page 73).
The Michaelis constant is also the inverse of the affinity of substrate for an
enzyme. In other words, a small Km indicates a high affinity meaning that Vmax
will be approached quickly, and the inverse is also true. The value of Km is also
dependent on the conditions in which the enzymatic reaction occurs, such as
temperature and pH.
In order to determine the constants in the equation, a series of enzyme assays
are run in the laboratory at various concentrations of substrate. The reaction rate
is measured at time 0 and then reaction rate can be plotted against [s]. Using non-
linear regression of the MichaelisMenten equation, Vmax and Km can be
obtained.
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Drugreceptor dissociation constant
and affinity
[D][R]
Kd =
[DR]
1
Affinity =
Kd
Kd = dissociation constant
D = drug (sometimes stated as a Ligand [L])
R = receptor
Units
Explanation
77
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78 Section 2: Pharmacology & Part 2b: Pharmacodynamics
high concentrations. This explains why affinity is the reciprocal of the dissoci-
ation constant.
Note that pKa is the particular dissociation constant for acidbase reactions
(refer to page 157).
2. Describe how knowledge of affinity can help in the design of new drugs.
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Therapeutic index
TD50
TI =
ED50
TI = therapeutic index
TD50 = toxic dose: the dose of drug that causes a toxic response in 50% of the
population
ED50 = effective dose: the dose of drug that is therapeutically effective in 50% of
the population.
Units
Fraction.
Explanation
The therapeutic index refers to the relationship between a particular drugs toxic
and therapeutic dose. It is calculated as the ratio between the two, the latter being
the dose that produces a clinically desired or effective response.
In animal studies, the toxic dose (TD50) may be substituted for the lethal dose
(LD50) the dose of drug that causes death in 50% of the population.
1. Give examples of drugs that have a narrow or wide therapeutic index, and
describe the concerns related to this.
Warfarin (2:1), digoxin (2:1) and gentamicin (2:1) all have a narrow therapeutic
index. Remifentanil (33,000:1) and diazepam (100:1) have wide therapeutic
indices.
For drugs with a narrow therapeutic index, small differences in the dose
administered or plasma concentration may have serious adverse events. This
79
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80 Section 2: Pharmacology & Part 2b: Pharmacodynamics
may be considered so serious that daily blood tests are warranted in order to
calculate the daily dose administered.
Conversely, drugs with a wider therapeutic index are regarded as more giving;
however, this does not account for the fact that drugs such as remifentanil can
have lethal side effects such as apnoea even within safe doses.
To overcome this, another term is used to denote the safety of the drug: margin
of safety (MOS). To calculate this, a ratio is taken of the dose that is just within
the lethal range (LD01) to the dose that is 99% effective (ED99). If the MOS is less
than 1, extreme caution should be taken.
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Cardiac output and cardiac index
CO = HR SV
And
CO
CI =
BSA
Units
CO l=min:
CI l=min=m2 :
Explanation
Cardiac output is the volume of blood pumped per minute by each ventricle of
the heart. The cardiac output is principally determined by the stroke volume
(refer to page 83) and the heart rate, and thus alterations in either of these
parameters will change the cardiac output.
81
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82 Section 3: Physiology & Part 3a: Cardiovascular
2. How can knowledge of the cardiac output equation be used in clinical anaes-
thetic practice?
Cardiac output monitors are routinely used during anaesthesia for major surgery
to guide the response to fluids. For example, if the cardiac output is found to be
lower than normal, a fluid challenge can be given and the resulting effects on the
stroke volume can be monitored. If stroke volume increases, this will have a
proportional effect on the cardiac output. If the stroke volume remains
unchanged and the heart rate is normal, then it is likely that the low cardiac
output is unrelated to the filling status of the ventricles.
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Stroke volume
SV = EDV ESV
SV = stroke volume
EDV = end diastolic volume
ESV = end systolic volume
Units
ml.
Normal in 70 kg man = 7080 ml (range 55100 ml).
Explanation
The stroke volume is the volume ejected from the ventricle with each myocardial
contraction. It may be estimated using an echocardiogram, by subtracting the
volume of blood in the ventricle pre- (EDV) and post- (ESV) contraction, or by
pulse contour analysis.
Stroke volume is dependent on the heart rate, contractility, preload and after-
load, and knowledge of Starlings law of the heart is fundamental to its under-
standing: The energy of contraction of a cardiac muscle fibre, like that of a skeletal
muscle fibre, is proportional to the initial fibre length at rest.
Stroke volume is also used to calculate the ejection fraction (see page 87).
In a similar manner to cardiac index (refer to page 81), stroke volume index
may be used to relate stroke volume to an individuals size.
SVI = SV/BSV
83
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84 Section 3: Physiology & Part 3a: Cardiovascular
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Ventricular stroke work and index
Units
Explanation
The stroke work describes the work done by each ventricle to eject a volume
(stroke volume) of blood and is used as a surrogate for contractility. The force
applied to the volume of blood is the intraventricular pressure, which as kinetic
energy is assumed to be negligible, is substituted for:
(1) mean systolic aortic pressure (afterload) minus left atrial pressure (preload)
in the case of the left ventricle, and
(2) mean pulmonary artery pressure minus right atrial pressure in the case of the
right ventricle.
The factor 0.0136 is used to convert pressure and volume to units of work.
A pressurevolume diagram is used to depict stroke work, designated by the
area within the pressurevolume loop.
85
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86 Section 3: Physiology & Part 3a: Cardiovascular
SV = 70 ml
MSAP = 100 mmHg
LAP = 10 mmHg
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Ejection fraction and fractional area change
EF = SV EDV
And
(EDA ESA)
FAC =
EDA
EF = ejection fraction
SV = stroke volume
EDV = end diastolic volume
FAC = fractional area change
EDA = end diastolic area
ESA = end systolic area
Units
Percentage (%)
Normal EF > 55%
Normal FAC > 35%
Explanation
The ejection fraction is the volumetric fraction of blood ejected from the ventricle
with each contraction. As stroke volume is calculated from end diastolic volume
minus end systolic volume, the equation may be given as:
(EDV ESV)
EF =
EDV
Ejection fraction is commonly used as a prognostic indicator in acute and chronic
heart failure, although having a preserved ejection fraction does not mean
freedom from risk.
An alternative method used to assess left ventricular function is to calculate
fractional area change (FAC) using echocardiography. This utilizes manual plan-
imetry of the area circumscribed by the endocardium at end diastole (EDA) and
87
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88 Section 3: Physiology & Part 3a: Cardiovascular
1. Describe what happens to the ejection fraction in congestive cardiac failure (CCF).
CCF is the inability of the heart to maintain adequate perfusion of the tissues. As
the ventricle becomes less efficient, usually as a result of dilation (refer to
Laplaces law, page 24), the force of contraction decreases. As a result, the
EDV increases and so ejection fraction decreases.
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Coronary perfusion pressure and coronary
blood flow
CBF = CPP/CVR
Units
mmHg.
Explanation
Coronary perfusion pressure refers to the pressure gradient that drives coronary
blood flow, thus the two equations are closely interlinked. Notably in the case of
the left ventricle, it is the diastolic pressure that is the important determination of
coronary perfusion. In systole, the myocardial blood vessels are compressed and
twisted by the cardiac contractions, and blood flow is negligible. These phasic
changes are less pronounced on the right side, due to lesser forces of contraction.
Coronary blood flow is typically 250 ml/min (0.8 ml/min/g of heart muscle) in
a 70 kg adult at rest, representing 5% of cardiac output. As cardiac arterial oxygen
extraction is 80% (cf. 25% for the rest of the body), increased oxygen consump-
tion must be met by an increase in coronary blood flow, which may increase
fivefold during exercise. The equation is analogous to the electrical equation
V = IR (refer to Ohms law, page 28), and allows us to see why any increase in
coronary vascular resistance can lead to devastating effects.
89
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90 Section 3: Physiology & Part 3a: Cardiovascular
1. Describe the effects of aortic stenosis and atherosclerosis on coronary blood flow.
When the left ventricle starts to fail, there is a decrease in the proportion of blood
ejected during systole (ejection fraction refer to page 87), which in turn results
in an increase in LVEDP. Using the equation, it is easy to see how CPP and CBF
may fall as a result. Initially, CBP may be ameliorated by reflex systemic vaso-
constriction, but this will result in an increase in pressure load and oxygen
demand.
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Bazetts formula QT interval corrected
QT
QTc = pffiffiffiffiffiffi
RR
Units
Time = ms.
Explanation
91
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The Fick principle cardiac output
measurement
VO2
CO =
C a O2 C v O2
CO = cardiac output
VO2 = oxygen consumption (ml/min)
CaO2 = arterial oxygen concentration
CvO2 = venous oxygen concentration
Units
l/min.
Explanation
The Fick principle (Adolf Eugen Fick, 1870), otherwise known as the Inverse Fick
equation, allows the measurement of cardiac output. Its underlying principle is
that the blood flow to an organ can be calculated using an indicator material if we
know:
(1) the amount of indicator material taken up by the organ per unit time;
(2) the concentration of indicator material in the arterial blood supplying
(entering) the organ; and
(3) the concentration of indicator material in the venous blood leaving the organ.
In this case, the indicator is oxygen, and so the Fick principle can be usefully
applied in normal clinical practice.
Initially, Ficks equation was used to calculate oxygen consumption in the
lungs (see below), but because pulmonary blood flow is equal to right ventricular
output, the equation can be rearranged to give cardiac output as above.
92
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Equation 3a.7: The Fick principle cardiac output measurement 93
Derivation
= CO C v O2
= CO C a O2
(3) amount of oxygen uptake by blood as it passes through the lungs is the
difference between arterial and venous concentrations
= (CO C a O2 ) (CO C v O2 )
(4) in steady state, oxygen uptake by pulmonary blood flow is equal to the removal
of alveolar oxygen:
VO2 = CO (C a O2 C v O2 )
(6) therefore:
VO2
CO =
C a O2 C v O2
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The Fick equation oxygen uptake
measurement
VO2 = CO (C a O2 C v O2 )
CO = cardiac output
VO2 = oxygen consumption (ml/min)
CaO2 = arterial oxygen concentration
CvO2 = venous oxygen concentration
Units
ml/min.
Explanation
The Fick equation (Adolf Eugen Fick, 1870) tells us the rate of oxygen uptake
from alveolar gas. Under aerobic conditions, oxygen is consumed to generate
energy, thus VO2 corresponds to metabolic rate. VO2max (maximal oxygen
uptake) is the maximal capacity of an individual to utilize oxygen. It is reached
when oxygen consumption remains at a steady state despite an increase in
workload.
VO2 can be directly measured using the analysis of respiratory gases (as seen in
cardiopulmonary exercise testing), or derived from cardiac output and arterial
venous oxygen contents.
The concept for VO2 was first purported in 1870, when Fick stated that the rate
at which the circulation absorbs oxygen from the lungs, must equal the change in
oxygen concentration in the pulmonary blood multiplied by pulmonary blood
flow.
NB: As pulmonary blood flow is equal to right ventricular output, the equation
can be rearranged to give cardiac output (see Fick principle for cardiac output
page 192).
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Equation 3a.8: The Fick equation oxygen uptake measurement 95
Derivation
= CO C v O2
= CO C a O2
(3) amount of oxygen uptake by blood as it passes through the lungs is the
difference between arterial and venous concentrations
= (CO C a O2 ) (CO C v O2 )
(4) in steady state, oxygen uptake by pulmonary blood flow is equal to the removal
of alveolar oxygen:
VO2 = CO (C a O2 C v O2 )
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Mean arterial pressure
Units
mmHg.
Explanation
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Equation 3a.9: Mean arterial pressure 97
At normal heart rates, MAP can therefore be approximated using the following
equations.
1
MAP = DBP + PP
3
where DBP = diastolic blood pressure; SBP = systolic blood pressure; PP = pulse
pressure.
1. A septic patient on the intensive care unit has a blood pressure of 82/37 mmHg
and a heart rate of 75 bpm. Approximate their mean arterial pressure.
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Venous return
PV PRA
VR =
RV
VR = venous return
PV = venous pressure
PRA = right atrial pressure
RV = venous resistance
Units
ml/min.
Explanation
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Equation 3a.10: Venous return 99
(i) Deep inspiration, such as that of the valsava manoeuvre, increases resistance
in the thoracic vena cava, and thus decreases venous return (VR).
(ii) Decreased venous compliance (due to increased sympathetic activity)
increases central venous pressure and promotes venous return indirectly
by augmenting cardiac output through the FrankStarling mechanism.
(iii) Laparoscopic surgery and gross insufflation of the abdomen compresses the
abdominal vena cava, and thus decreases venous return through increased
RV. This causes a detrimental effect on cardiac output.
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Total blood volume
Vp
TBV =
1 Hct
Or rearranged
V p 100
TBV =
100 Hct
Units
ml or l.
Explanation
Total blood volume can be indirectly determined if the plasma volume and
haematocrit are known.
The plasma volume in litres can be estimated using the following equation:
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Equation 3a.11: Total blood volume 101
1. Calculate the plasma volume and total blood volume for this patient in the
intensive care unit:
Weight 75 kg
Haematocrit 0.320
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Systemic vascular resistance
!
MAP CVP
SVR = 80
CO
Units
dyns/cm5.
Explanation
MAP
SVR =
CO
Importantly, although SVR is calculated from MAP and CO, it is not determined
by either of these variables. While in the above equation SVR is the dependent
variable, physiologically SVR and CO are the independent variables, and MAP the
dependent variable.
The figure of 80 is used as a correction factor to change mmHg to dyns/cm5.
SVR may be indexed (SVRI) to body surface area (BSA) by substituting CO in
the equation for cardiac index (CI). Normal range is 19702390 dyns/cm5/m2.
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Equation 3a.12: Systemic vascular resistance 103
Decrease Increase
Anaemia (through reduced viscosity) Severe pre-eclampsia
Fever (through increased O2 demand) Essential hypertension
Sepsis Smoking
Anaphylaxis Diabetes
Most general anaesthetic agents Obesity
2. How does knowledge of the equation assist in the management of a critically ill
hypotensive patient?
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Uterine blood flow
UPa UPv
UBF =
UVR
Units
ml/min.
Explanation
The equation for uterine blood flow is analogous to Ohms law V = IR (refer to
page 28) where:
V = UPa UPv
I = UBF and
R = UVR
Maintaining an adequate flow (approximately 500700 ml/min at term) is funda-
mental, as the uterine blood flow supports the foeto-placental circulation upon
which the developing foetus is entirely reliant. In a normal healthy placenta,
uterine blood flow can decrease by about 50% before foetal distress, diagnosed by
the presence of foetal acidosis, is detected.
Importantly, uterine blood flow is not autoregulated, and thus wholly reliant
on the pressure gradient (UPa UPv) and the local resistance (UVR). Any drugs
that alter either of these will affect uterine blood flow.
104
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Equation 3a.13: Uterine blood flow 105
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StewartHamilton equation
CO = cardiac output
Vinjectate = volume of injectate
k = correction factor
Tblood = temperature of blood
Tinjectate = temperature of injectate
TB dt = integral of area under temperature/time curve
Units
l/min.
Explanation
There are several methods used to calculate cardiac output. The thermodilution
technique utilizes the StewartHamilton equation (George Neil Stewart, 1897 and
William Hamilton, 1932). It is based on the principle that the cardiac output is
equal to the amount of an indicator injected divided by its average concentration
in the arterial blood after a single circulation through the heart.
The denominator of the equation equates to the quantity of injectate and the
numerator refers to its concentration.
106
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Equation 3a.14: StewartHamilton equation 107
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Oxygen delivery
Units
ml/min.
Explanation
108
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Equation 3a.15: Oxygen delivery 109
Hypoxia, the deficiency of oxygen at the tissue level, may be caused by any
number of factors that affect the above equation.
(1) Decreased arterial oxygen content as a consequence of:
(i) anaemic hypoxia decreased oxygen carrying capacity secondary to low
haemoglobin levels, or increased abnormal forms of haemoglobin that
are unable to bind to oxygen;
(ii) hypoxic hypoxia a decrease in the amount of oxygen bound to
haemoglobin;
(2) decreased cardiac output (stagnant hypoxia), normally secondary to inad-
equate circulating volume (hypovolaemia) or inadequate cardiac function
(cardiogenic shock).
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Oxygen extraction ratio
O2 ER = VO2 /DO2
Or otherwise defined as
O2 ER = C a O2 C v O2 / C a O2
Units
Nil it is a ratio.
Explanation
The oxygen extraction ratio is the ratio of oxygen uptake to oxygen delivery. It
therefore represents the fraction of oxygen delivered to the microcirculation and taken
up by the metabolizing cells. Different organs utilize different amounts of oxygen;
however, globally the normal O2ER is 0.20.3, i.e. 2030% of oxygen is utilized. Organs
with high extraction ratios include the heart (60%) and the brain (35%).
1. Describe how the oxygen extraction ratio may alter in critical illness.
In normal health, systemic VO2 reflects the bodys metabolic demands and
remains relatively independent of DO2. In critical illness, if the DO2 cannot
match the VO2, the increased metabolic demands will initially be met by increas-
ing the oxygen extraction ratio.
110
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Equation 3a.16: Oxygen extraction ratio 111
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Oxygen content equation
Units
ml O2/dl.
Explanation
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Equation 3a.17: Oxygen content equation 113
2. Describe the benefit of using hyperbaric oxygen for carbon monoxide poisoning.
Carbon monoxide (CO) has a greater affinity to haemoglobin than oxygen, and
consequently in the presence of CO, oxygen content decreases.
Normally the amount of dissolved oxygen in the blood contributes very little to
the overall oxygen content (< 1.5%); however, if a patient is subjected to
increased pressures in a hyperbaric chamber, their partial pressure of oxygen
increases. This in turn means that the dissolved oxygen contributes far more to
the CaO2. If the pressure is increased from one to three atmospheres, the
dissolved oxygen alone could be adequate to meet the patients metabolic
requirements.
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The dilution principle measurement of fluid
compartment volume
M
V=
C
V = volume
M = mass
C = concentration
Units
ml.
Explanation
114
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Diffusing capacity
VCO
DL CO =
PA CO
Units
ml/min/mmHg.
Normal = 25 ml/min/mmHg.
Explanation
Diffusing capacity is denoted by DL, which stands for diffusion lung, followed by
the chemical species. It is also known as the transfer factor (TL), and commonly
uses the gas carbon monoxide.
The diffusing capacity is the ability of the respiratory membrane to exchange a
gas between the alveoli and the pulmonary blood. It is the volume of a gas that
diffuses across the membrane per minute for each mmHg partial pressure
difference. For a given gradient in partial pressure of gas, the higher the diffusing
capacity, the larger the amount of gas transferred into the lung per unit time.
The single breath method is the commonly used test to determine diffusing
capacity. Carbon monoxide is used as the gas for this test, because oxygen
diffusion into the pulmonary capillaries may be perfusion-limited, whereas CO
is solely diffusion-limited. Furthermore, as CO rapidly binds to haemoglobin, the
partial pressure of CO in capillary blood (PcCO) is negligible and can be
neglected in calculations (PACO PcCO = PACO).
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116 Section 2: Physiology & Part 3b: Respiratory
DL CO = 40/0.7
= 57 ml/min/mmHg
2. What gas is commonly used to measure the diffusing capacity of the lung?
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Compliance
volume
Compliance =
pressure
Units
ml/cmH2O.
Normal total lung compliance = 100 200 ml/cmH2O.
Explanation
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118 Section 2: Physiology & Part 3b: Respiratory
3. Calculate the static compliance of a critically ill patient from the following:
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Bohr equation
Units
Nil it is a ratio.
Normal ratio of dead space to tidal volume at rest is 0.20.35.
Explanation
The Bohr equation (Christian Bohr, 18551911) is used to derive the physio-
logical dead space. It is given as a ratio of dead space to tidal volume. Its
derivation (see below) is based on the fact that only ventilated alveoli involved
in gas exchange will produce CO2, and none from the dead space.
Physiological dead space differs from anatomical dead space (measured by
Fowlers method) as it measures the volume of the lung that does not eliminate
CO2, and thus includes alveolar dead space. In health, however, the volumes are
almost identical.
In practice, PaCO2 can be substituted for PACO2 and end-tidal CO2 for PECO2
to use this equation.
119
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120 Section 2: Physiology & Part 3b: Respiratory
Derivation
(1) Tidal volume (Vt) is made up of alveolar volume (VA) and dead space
volume (Vd)
V t = V A +V d
And rearranging
VA = Vt Vd
V t FE = V A FA
(FE = fraction of expired CO2, FA = alveolar fraction of CO2).
(3) If we substitute in
V t F E = (V t V d ) F A
V d /V t = (F A F E )/F A
NB: As the PCO2 in alveolar gas and arterial blood are almost the same in normal
health, the equation may be written as
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Alveolar ventilation equation
!
VCO2
VA = k
PA CO2
Commonly rearranged to
VCO2
PA CO2 =
VA
Units
Explanation
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122 Section 2: Physiology & Part 3b: Respiratory
1. What would happen to a patients arterial carbon dioxide if they were adminis-
tered a high dose of opioids?
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Alveolar gas equation
NB : Pi O2 = Fi O2 (PATM PH2 O)
Units
Units of pressure.
(The standard SI unit for pressure is the pascal (Pa); however, several other
units are commonly used: bar, atmospheres, mmHg, cmH2O.)
Explanation
The alveolar gas equation is used to calculate the partial pressure of oxygen in the
alveoli (PAO2) using data that are practically measured. It is essential to under-
standing any PaO2 value and Alveolararterial (Aa) gradient, and in assessing if
the alveoli are adequately transferring oxygen into the pulmonary circulation.
The equation assumes:
(1) inspired gas contains no CO2 or water;
(2) the alveolar and arterial partial pressures of CO2 are in equilibrium;
(3) the alveolar gas is saturated with water;
(4) the inspired and alveolar gases obey the ideal gas law.
RQ varies with diet (refer to page 136).
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124 Section 2: Physiology & Part 3b: Respiratory
1. A patient in the resuscitation bay, breathing 50% oxygen, has the following
arterial blood gas results:
Pa O2 14 kPa
Pa CO2 6.4 kPa
Calculate their Alveolararterial (Aa) gradient
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Helium dilution technique
C1 C2
V2 = V1
C2
Units
Explanation
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126 Section 2: Physiology & Part 3b: Respiratory
Derivation
(1) The spirometer contains a known volume of gas (V1) with a known concen-
tration of helium in it (C1).
(2) Therefore, the amount of helium present in the spirometer before equilibrium
= C1 V 1
(3) Once the patient starts breathing, the helium concentration will drop as it gets
diluted within the patients lungs and the spirometer. Therefore, the amount of
helium present after equilibrium
= C 2 (V 1 + V 2 )
(4) Thus
V 2 ( = FRC)
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Spirometry: forced expiration
FEV 1
Ratio =
FVC
Units
Nil it is a ratio.
Normal = .80 (= 80%).
Explanation
This simple equation allows one to distinguish between restrictive and obstructive
lung diseases.
In obstructive disease, for example asthma and chronic obstructive airways
disease (COAD), while the FVC may be normal or mildly decreased, FEV1 is far
more reduced due to increased airway resistance to expiratory flow. This gives a
low FEV1/FVC, and typically values of < 80% are demonstrated.
In restrictive disease such as pulmonary fibrosis, the FVC and FEV1 are both
decreased, and consequently the FEV1/FVC value will be normal or increased.
1. A breathless patient in the clinic presents with the following spirometry results:
FEV1 = 2.5 l, FVC = 4 l. Suggest whether this is a normal, obstructive or restrictive
picture.
From the equation above, 2.5/4 = 63%.
Therefore, this is an obstructive picture, and may represent asthma or COAD.
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Lung volumes and capacities
5 IRV
2500 ml VC
4500 ml
4
Volume (I)
TV TLC
500 ml 6000 ml
3
ERV FRC
2 1500 ml 3000 ml
1 RV
1500 ml
0
0 5 10 15 20 25 30
Time (s)
See below.
Units
ml.
Explanation
These refer to the volume of gas associated with different phases of the respira-
tory cycle. Importantly:
(1) lung volumes are discrete measurements of specific entities;
(2) lung capacities are two or more volumes added together.
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Equation 3b.8: Lung volumes and capacities 129
As seen from the above diagram, there are multiple ways in which these can be
calculated.
(i) Total Lung Capacity (TLC) = Inspiratory Reserve Volume (IRV) +
Tidal Volume (TV) + Expiratory Reserve Volume (ERV) + Residual
Volume (RV).
(ii) Functional Residual Capacity (FRC) = ERV + RV.
(iii) Vital Capacity (VC) = IRV + TV + ERV.
(iv) Tidal Volume (TV) = Alveolar Volume (VA) + Anatomical dead space
(Vd) (normal = 7 ml/kg).
(v) Inspiratory Capacity (IC) = IRV + TV.
(vi) Expiratory Capacity = TV + ERV.
(NB: TV interchangeable, elsewhere stated as Vt.)
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Respiratory quotient and respiratory
exchange ratio
RQ = VCO2 /VO2
RQ = respiratory quotient
VCO2 = carbon dioxide exhaled
VO2 = oxygen uptake
Units
A quotient is, by its nature, dimensionless. The two gases must have the same
units and in quantities proportional to the number of molecules (e.g. ml/kg/min).
However, they cancel each other out to give RQ.
Explanation
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Equation 3b.9: Respiratory quotient and respiratory exchange ratio 131
At complete rest, ones VCO2 and VO2 will be similar to cellular carbon dioxide
production and oxygen consumption (QCO2 and QO2, respectively). As one
starts to exercise gently, hyperventilation will increase both oxygen consumption
and carbon dioxide production, although if we say the metabolic source has not
altered, it will still be in the same ratio.
At anaerobic threshold (lactate threshold), where anaerobic ATP synthesis
supplements aerobic ATP synthesis, lactic acid is produced, excess CO2 is
exhaled, and consequently the RQ increases as CO2 production exceeds oxygen
uptake.
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Shunt equation
QS C c O2 C a O2
=
QT C c O2 C v O2
Units
Explanation
The shunt equation quantifies the extent that venous blood bypasses oxygenation
in the pulmonary capillaries of the lung.
In normal health, blood from the bronchial veins (draining the lung paren-
chyma), and the Thebesian veins (draining cardiac muscle), represents a physio-
logical shunt of approximately 5% of cardiac output. This shunted fraction of
total pulmonary blood flow will increase as more blood flows through non-
ventilated segments of lung whatever the underlying cause.
Hypoxia caused by shunted blood cannot be remedied by breathing 100%
oxygen, as the shunted blood bypasses ventilated alveoli.
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Equation 3b.10: Shunt equation 133
Derivation
(1) Total pulmonary blood flow is made up of blood passing through the pulmon-
ary capillaries (Qc) and blood that has bypassed the pulmonary capillaries (Qs)
QT = QS +Qc
(2) Qc can be calculated by subtracting the shunted blood (QS) from the total blood
flow (QT).
Qc = QT QS
(3) If we add the oxygen content to the equation first equation, we get the oxygen
content of QT.
QT C a O2 = QS C v O2 +((QT C c O2 ) (QS C c O2 ))
(4) Multiply out of brackets, and get QS and QT terms on the same side
QS (C c O2 C v O2 ) = QT (C c O2 C a O2 )
QS C c O2 C a O2
=
QT C c O2 C v O2
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Pulmonary vascular resistance
PAP PAWP
PVR = 80
CO
Units
dyns/cm5 or mmHgmin/l.
(The latter of these are known as Wood units. They are used for ease of deriving
pressure (mmHg) and cardiac output (l/min).)
Normal range 20130 dyns/cm5 or 0.251.6 Woods units.
Explanation
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Equation 3b.11: Pulmonary vascular resistance 135
PAP 15 mmHg
LAP 5 mmHg
CO 5 l=min
tahir99 - UnitedVRG
vip.persianss.ir
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Renal filtration fraction
GFR
FF =
RPF
FF = filtration fraction
GFR = glomerular filtration rate
RPF = renal plasma flow
Units
Nil.
Explanation
The renal filtration fraction gives the proportion of plasma filtered at the glom-
eruli. Of the total renal blood flow (1 l/min), only the plasma (600 ml/min) has
the potential to be filtered. In normal health, with a GFR of 125 ml/min, this
approximates to 20%.
Renal artery stenosis reduces renal blood flow, and thus in order to maintain the
normal renal function, glomerular filtration rate increases and consequently renal
filtration fraction increases.
Thiazide and loop diuretics decrease the filtration fraction.
136
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Renal clearance and CockcroftGault formula
Ux V
Cx =
Px
Cx = renal clearance of x
Ux = urine concentration of x
V = urine flow
Px = plasma concentration of x
Units
ml/min.
Explanation
The clearance of any substance excreted by the kidney is the volume of plasma
that is cleared of the substance per unit time. This is analogous to the clearance
equation for any drug, UV/P (refer to page 55).
Clearance represents a theoretical volume of plasma cleared of the substance
per unit time; however, physiologically, no quantity of plasma is completely
cleared of a substance as it passes through the kidney.
Creatinine is routinely used clinically to assess clearance, and thus give an
indication of renal function through an approximation of the glomerular filtra-
tion rate (GFR). It is freely filtered, not reabsorbed, synthesized or metabolized by
the kidney and therefore its plasma levels remain relatively constant. However,
the peritubular capillaries also actively secrete creatinine such that creatinine
clearance overestimates actual GFR by 1020%, and in practice, GFR is usually
calculated using, for example, the CockcroftGault formula (Donald Cockcroft,
Henry Gault, 1976):
(140 age) Mass K
eC cr =
Creatinineserum
K = constant (1.23 in males, 1.04 in females)
Mass (kg)
Creatinine (mol/l)
137
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138 Section 3: Physiology & Part 3c: Renal
1. Calculate the creatinine clearance (CCr) for the following patient in the intensive
care unit:
C Cr = (UCr V Cr )/PCr
= (1 1440)/0.01
= 144,000 in 24 hours
= 100 ml/min
Age 67
Weight 89
Serum creatinine 387
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Starlings equation rate of filtration
Jv = k (Pc + i ) (Pi + c )
Units
ml/min.
Explanation
The Starling equation (Ernest Starling, 1896) illustrates the role of hydrostatic
and oncotic forces (the so-called Starling forces) in the movement of fluid across
capillary membranes.
The first part of the equation describes the forces favouring filtration and the
second half describes the forces opposing filtration. Therefore, net filtration is
proportional to net driving force.
The filtration coefficient is the constant of proportionality. A high value
indicates a highly water-permeable capillary, and vice versa.
The forces governing glomerular filtration are the hydrostatic pressure gradients
and the oncotic pressure gradients. These can be described as the forces favouring
filtration (glomerular capillary hydrostatic pressure plus oncotic pressure in the
139
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140 Section 3: Physiology & Part 3c: Renal
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Ficks law of diffusion
A
Vgas D (P1 P2 )
T
And
Sol
D p
MW
Units
ml/min.
Explanation
Ficks law (Adolf Fick, 1855) describes diffusion of a gas through tissues and can,
if required, be used to solve the diffusion coefficient. In clinical terms, it is
normally used to describe the movement of oxygen and carbon dioxide down a
concentration gradient. Remember that diffusion is always a passive process that
requires no energy.
The equation states that:
(1) the rate of diffusion of a gas through tissues is proportional to the:
surface area (A),
difference in gas partial pressure between the two sides (P), and
solubility of gas in the tissue (Sol); and
141
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142 Section 3: Physiology & Part 3c: Renal
1. Describe the factors that may affect the diffusion of a gas across the bloodgas
barrier.
If the gas in question remained the same gas, then this would not alter factors
relating to the diffusion constant (solubility and molecular weight). Altering
factors would thus include the area and thickness of the bloodgas barrier (such
as fibrosis), and difference in partial pressure of gas (such as alveolar hypoxia).
2. Using Ficks Law, what features in the lung make diffusion more efficient?
The surface area (A) is very large due to the presence of millions of alveoli.
The difference in partial pressure of the gases is maintained by breathing and
pulmonary blood flow.
The alveolar walls are only one cell thick (T).
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Osmolality/osmolarity and the osmolar gap
Units
Osmolality (mOsmol/kg).
Osmolarity (mOsmol/l).
The normal osmolality of extracellular fluid is 280295 mOsmol/kg.
Explanation
143
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144 Section 3: Physiology & Part 3d: Cellular, biochemical and acidbase
1. Calculate the osmolar gap for this patient presenting in the Emergency Depart-
ment with a decreased level of consciousness, and describe the result.
Hb 10.4 g/dl
Na 134 mmol/l
K 3.7 mmol/l
HCO3 23 mmol/l
Urea 4.4 mmol/l
Creatinine 74 mmol/l
Glucose 12.1 mmol/l
Serum osmolality 324 mOsm/l
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Morse equation and osmotic pressure
= iRTM
= osmotic pressure
R = universal gas constant
T = absolute temperature
M = molar concentration in mol/l
i = vant Hoff factor (empirical constant related to the degree of dissociation of
the solute).
Units
Explanation
145
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146 Section 3: Physiology & Part 3d: Cellular, biochemical and acidbase
When isotonic fluids are administered, water movement in and out of the cells is
negligible. However, when hypotonic solutions such as 0.45% sodium chloride
are given, water will move in to the cells until the osmotic pressure within the cell
opposes any further movement. However, this may result in cell lysis, which is
especially important in those patients with brain injuries.
Conversely, hypertonic solutions will encourage fluid out of the intracellular
and interstitial spaces in to the intravascular compartment until the osmotic
pressure opposes this. This may be beneficial in some cases, for example to
reduce cerebral oedema, but can cause circulatory overload and cardiac failure
in susceptible patients.
In normal plasma, the plasma proteins are the major colloids present (particles of
large molecular weight). Because the colloids are solutes, they contribute to the
total osmotic pressure. This component is referred to as the colloid osmotic
pressure or oncotic pressure.
3. Use the vant Hoff equation to calculate the osmotic pressure for this typical
plasma sample:
T 310K 37 C
R 0 082 latm=molK
i 1 because plasma proteins do not dissociate
M 0.280 mol=l
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Anion gap
Cations:
[Na+] = concentration of sodium ions
[K+] = concentration of potassium ions
Anions:
[Cl] = concentration of chloride ions
[HCO3] = concentration of bicarbonate ions
(NB: *[K+] may be omitted in some formulae as its concentration is relatively low
compared to the other three ions and typically does not change much.)
Units
Explanation
147
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148 Section 3: Physiology & Part 3d: Cellular, biochemical and acidbase
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Goldman equation
Em = membrane potential
Pi = membrane permeability for the ion in question (Na, K, Cl)
[ion]i = intracellular concentration of the ion
[ion]o = extracellular concentration of the ion
R = universal gas constant
T = temperature
F = Faradays constant
Units
mV.
Explanation
149
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150 Section 3: Physiology & Part 3d: Cellular, biochemical and acidbase
1. What are the resting membrane potentials for the following cell types?
Answer
Skeletal muscle cells 95 mV
Smooth muscle cells 60 mV
Astroglia 80 to 90 mV
Neurons 60 to 70 mV
Cardiac myocyte 90 mV
Cardiac pacemaker cell 60 mV
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GibbsDonnan effect
Units
Nil.
Explanation
The GibbsDonnan effect (Josiah Gibbs, Frederick Donnan, 1911) describes the
behaviour of charged particles across a semipermeable membrane. Because some
particles cannot diffuse across the membrane (e.g. proteins), their electrostatic
presence will result in the asymmetric distribution of permeable ions. In vivo, this
mainly results in the movement of sodium and chloride ions between the
intravascular and interstitial body compartments.
Ultimately, as described in the equation, the diffusible anions and cations are
distributed across the two sides of the membrane so that:
(1) the products of their concentrations are equal, and
(2) the sum of the permeable and impermeable anions on either side is equal to
that of the permeable and impermeable cations on either side.
This ultimately achieves electro-neutrality across both sides of the membrane.
The balance between the chemical and electrostatic forces produces an elec-
trical potential difference that can be calculated using the Nernst equation (refer
to page 153).
151
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152 Section 3: Physiology & Part 3d: Cellular, biochemical and acidbase
Critically ill patients requiring renal replacement therapy are often prescribed
haemodialysis. Here, the dialysis solution is carefully regulated to dictate the
movement of ions between the plasma and the dialysate.
Sodium movement is principally regulated by the ionic activity rather than the
total sodium concentration. Plasma proteins are negatively charged and not
diffusible through the dialysis membrane thereby setting up an electrostatic
gradient across the membrane. The GibbsDonnan effect dictates that sodium,
as the principle cation, will cross the membrane into the plasma to restore
electrochemical neutrality.
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Nernst equation
RT
[C]o
E= ln
zF [C]i
E = equilibrium potential
R = universal gas constant
T = temperature
z = valency (the number of valence bonds a given atom can form with one or
more other atoms)
F = Faradays constant
[C]o = concentration of ion outside the cell
[C]i = concentration of ion inside the cell
Units
mV.
Explanation
153
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154 Section 3: Physiology & Part 3d: Cellular, biochemical and acidbase
1. Describe the Nernst potential for potassium and sodium in a cell in its resting
state.
At rest, excitable cell membranes such as those found in cardiac myocytes are
nearly fully permeable to potassium (K+). Therefore, the equilibrium potential for
K+ is comparable to the cells resting membrane potential (RMP) of approxi-
mately 90 mV.
Because of this, changes in the extracellular potassium concentration can have
a profound effect on the RMP. In cardiac myocytes, an elevated serum potassium
concentration can markedly increase the likelihood of the cell depolarizing,
thereby increasing the risk of arrhythmias.
As the same cell membranes are comparatively impermeable to sodium (Na+),
this ion has an equilibrium potential of approximately +80 mV. As Na+ move-
ment across the cell membrane is much more dependent on ion channels, a
change in the extracellular concentration is much less likely to cause clinical
symptoms. This is manifest in the fact that the normal range of Na+ in clinical
practice is 45 times as large as that of K+.
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pH
pH = log[H+ ]
Units
Explanation
pH (Sren Sorensen, 1909), quoted as the negative logarithm of the hydrogen ion
concentration [H+], represents the activity of hydrogen ions within a given
solution. (The meaning of p is unclear, but probably refers to power.)
As the equation uses a negative logarithm, for each reduction by one in pH,
there is a 10-fold increase in [H+] activity. For example, a 0.1 unit fall in pH from
7.4 to 7.3 represents a 25% increase in [H+] activity.
The pH of pure water is about 7 at 25 C; acids have a pH lower than this, and
alkaline solutions have a pH higher than this. Most measured values lie in the
range from 0 to 14. However, within the body, the pH of various body compart-
ments is tightly regulated through homeostatic mechanisms. The normal range
for blood is 7.347.45, whereas gastric acid has a pH around 1.
155
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156 Section 3: Physiology & Part 3d: Cellular, biochemical and acidbase
pH
5.00
6.00
7.00
7.40
8.00
9.00
Answer
pH [H+] (nM/dl)
5.00 10,000
6.00 1,000
7.00 100
7.40 40
8.00 10
9.00 1
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pKa
pKa = logKa
Units
Nil.
Explanation
pKa represents the negative logarithmic measure of the acid dissociation constant
(Ka). The acid dissociation constant is the equilibrium constant for the dissoci-
ation of acidbase reactions and gives a quantitative measure of the strength of an
acid in a solution.
A given generic acid (HA) will dissociate into its conjugate base (A) and
hydrogen ions or proton [H+]. The chemical species are said to be in equilibrium
when their concentrations do not change with the passing of time:
HA A + H+
The dissociation constant is usually written as a quotient of the equilibrium
concentrations (in mol/l)
[A ][H+ ]
Ka =
[HA]
The lower the pKa, the higher the extent of dissociation and thus pH of the
solution.
The concept of pKa is important to understand in relation to membrane
permeability within the body. Most drugs exist as either weak acids or weak
bases and therefore in ionized and unionized forms depending on the pH of the
environment. In general, only the unionized form can cross the cell membrane.
157
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158 Section 3: Physiology & Part 3d: Cellular, biochemical and acidbase
Local anaesthetics are weak bases, such that they exist in ionized (BH+) and
unionized (B) forms. Their pKa defines the pH at which equilibrium is reached
between the two forms, and also determines the amount of local anaesthetic in
each form at any given pH.
At the physiological pH of 7.4, 25% of lignocaine (pKa 7.9) is in the unionized
form, and 15% of bupivacaine (pKa 8.1). It is this unionized form that is
important in determining the speed of onset for local anaesthetics, as this is the
form that crosses the nerve cell membrane.
This explains why the drug with the lower pKa (lignocaine), and consequently
more unionized in nature, will reach the target site and act more quickly.
Aspirin is a weak acid and so in the highly acidic environment of the stomach,
more of the unionized form exists, which enables the drug to cross the cell
membrane.
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Acidbase compensation simplified
Units
Nil.
Explanation
159
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160 Section 3: Physiology & Part 3d: Cellular, biochemical and acidbase
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HendersonHasselbalch equation
[A ]
pH = pKa + log
[HA]
Modified version to relate the pH of blood to constituents of the bicarbonate
buffering system.
[HCO3 ]
pH = pKa + log
[H2 CO3 ]
Or
[HCO3 ]
pH =
Pa CO2
Units
Explanation
161
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162 Section 3: Physiology & Part 3d: Cellular, biochemical and acidbase
(CO2) combines with water to form carbonic acid (H2CO3), which in turn rapidly
dissociates to hydrogen ions [H+] and bicarbonate (HCO3).
H2 O + CO2 H2 CO3 H+ + HCO3
(2) Formulate the dissociation constant (Kd) for the above equation.
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Cerebral perfusion pressure and intracranial
pressure
Units
mmHg.
Normal CPP: 7080 (range 50150) mmHg.
Normal ICP: 515 mmHg.
Explanation
163
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164 Section 3: Physiology & Part 3e: Neurological
2. How can knowledge of the CPP equation guide the management of a patient
with traumatic brain injury?
Following a head injury, cerebral blood flow is often decreased due to the effects
of raised ICP secondary to bleeding, the loss of normal autoregulation, and
hypovolaemia secondary to other injuries in the multiple-injured patient. In
order to prevent neuronal injury and secondary brain injury, the CPP must be
maintained above 70 mmHg.
The equation dictates that MAP should be appropriately maintained and ICP
controlled.
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Intraocular pressure
F
IOP = +PV
C
Units
mmHg.
Normal = 1020 mmHg.
Explanation
165
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166 Section 3: Physiology & Part 3e: Neurological
There are a number of ways that the eye can be affected when positioning a
patient in the prone position, all of which can cause catastrophic post-operative
blindness. These include inadvertent external pressure on the eye which may
cause the IOP to rise, venous engorgement which raises the CVP and PV, or
ischaemic optic neuropathy caused by hypotension.
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Binary classification tests and 2 2 tables
Outcome
Exposure Experienced disease Did not experience disease
Exposed a b
Unexposed c d
167
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Negative predictive value
TN
NPV =
(TN + FN)
Units
Percentage.
Explanation
The negative predictive value of a test allows one to ask of a clinical test: if the test
result is negative, what is the likelihood that this patient does not have the
disease? It is the probability that a patient truly does not have the condition if
a test is negative.
NPV, like PPV (positive predictive value) (refer to page 170), depends on the
prevalence of the disease in the population, as well as on the sensitivity and
specificity of the procedure used. Lowering the prevalence of true positives (TPs)
lowers the PPV. Increasing the prevalence will decrease the NPV.
168
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Equation 4.2: Negative predictive value 169
1. Calculate the negative predictive value of this new test for serum Legionella
antigens.
TN
NPV =
(TN + FN)
NPV = 131/(131 + 5)
= 96%
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Positive predictive value
TP
PPV =
(TP + FP)
Units
Percentage.
Explanation
The positive predictive value of a test allows one to ask of a clinical test: if the test
result is positive, what is the likelihood that this patient has the disease? It is the
probability that a patient is truly positive if a test is positive.
PPV and NPV (negative predictive value) (refer to page 168) depend on the
prevalence of the disease in the population, as well as on the sensitivity and
specificity of the procedure used. Lowering the prevalence of TPs lowers the PPV.
Increasing the prevalence will decrease the NPV.
170
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Equation 4.3: Positive predictive value 171
1. Calculate the positive predictive value of this new test for serum Legionella
antigens.
TP
PPV =
(TP + FP)
PPV = 32/(32 + 7)
= 82%
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Specificity
TN
Specificity =
(TN + FP)
TN = true negative
FP = false positive
Units
Percentage.
Explanation
Specificity describes a clinical tests ability to correctly identify patients who have
not got the disease. It is the proportion of true negatives correctly identified as
such.
If a test has a specificity of 75%, of those who do not have the disease, 75% will
correctly test negative (true negative), and 25% will be identified as having the
disease in its absence (false positive).
Ideally, a test needs to be both highly specific and sensitive (refer to page 174).
If a clinical test is highly sensitive but not very specific, many people will be
incorrectly identified as having the disease, when actually they do not.
172
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Equation 4.4: Specificity 173
1. Calculate the specificity for a new exhaled breath analyzer used to screen for the
presence of lung cancer.
TN
Specificity =
(TN + FP)
Specificity = 30 / (30 + 24)
= 56%
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Sensitivity
TP
Sensitivity =
(TP + FN)
TP = true positive
FN = false negative
Units
Percentage.
Explanation
Sensitivity measures the ability of a clinical test to correctly identify those patients
with the disease. In other words, it measures how sensitive the test is to picking up the
diseases presence. It is the proportion of true positives correctly identified as such.
An optimal screening test will have both a high sensitivity and specificity (refer
to page 172). However, there is an inverse relationship between the two measures:
improving one will decrease the other.
If a test has a sensitivity of 75%, of those whom have the disease, 75% will test
positive (true positive), and 25% will not be identified when they should test
positive (false negatives), i.e. they will be unidentified cases.
174
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Equation 4.5: Sensitivity 175
1. A new exhaled breath analyzer is used to screen for the presence of lung cancer.
Calculate the sensitivity of the test.
TP
Sensitivity =
(TP + FN)
Sensitivity = 32 / (32 + 5)
= 86%
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Relative risk
(a/(a + b))
RR =
(c/(c + d))
Or
IT
RR =
IC
Units
Nil.
Explanation
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Equation 4.6: Relative risk 177
1. From the 2 2 table, calculate the relative risk of cancer associated with
smoking.
Outcome
Exposure
Lung cancer No lung cancer
Smoker 28 (a) 72 (b)
Non-smoker 4 (c) 96 (d)
(a/(a + b))
RR =
(c/(c + d))
(28 / (28 + 72)
RR =
(4 / (4 + 96)
=7
You are seven times more likely to get lung cancer if you smoke.
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Relative risk reduction
ARR
RRR =
Ic
Units
Percentage.
Explanation
The relative risk reduction, calculated by dividing the absolute risk reduction
(ARR) by the control incidence, is the proportion by which the intervention
reduces the event rate. It can be more useful than ARR, as it not only accounts for
the effectiveness of a drug or treatment, but also for the relative chance of an
incident occurring in the absence of treatment.
178
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Equation 4.7: Relative risk reduction 179
1. 100 hypertensive men were given a new anti-hypertensive drug, and 100 hyper-
tensive men were given a placebo. The results were as below.
Outcome
Exposure
BP improved BP not improved
Given anti-hypertensive 80 20
Placebo 60 40
ARR
RRR =
Ic
RRR = 20/40 = .5
RRR = 50%
The incidence of hypertension was reduced from 40% with placebo to 20% with
treatment, i.e. by half.
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Absolute risk reduction
ARR = I T IC
Units
Percentage.
The equation above gives an absolute number, but can also be converted to
percentage.
Explanation
The absolute risk reduction is the difference in risk between the exposed group
and the unexposed group. ARR measures the impact of exposure.
180
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Equation 4.8: Absolute risk reduction 181
1. 100 hypertensive men were given a new anti-hypertensive drug, and 100 hyper-
tensive men given a placebo. The results were as below.
Outcome
Exposure
BP improved BP not improved
Given anti-hypertensive 80 20
Placebo 60 40
ARR = IT IC
ARR = 80/100 60/100
= 0.8 0.6
= 0.2 = 20%
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Accuracy of test
(TP + TN)
Accuracy =
Total
TP = true positive
TN = true negative
Total = total number
Units
Nil.
Explanation
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Equation 4.9: Accuracy of test 183
1. A new assay has been used to screen for Clostridium difficile in patients blood
samples. The results for 100 patients are as follows.
(TP + TN)
Accuracy =
Total
Accuracy = (34 + 30)/100
= 64%
This is not a very accurate test.
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Chi-squared test
(o e)2
c2 =
e
2 = Chi-squared
= sum of
o = observed number
e = expected number
Units
Nil.
Explanation
The Chi-squared test is a statistical hypothesis test used for comparing the
observed numbers in each cell of a 2 2 table with those we would expect if
there was no relationship between the two variables (i.e. if the null hypothesis is
true). It measures how well the observed (actual) distribution of data fits with the
expected distribution under the null hypothesis (no difference between results).
It is obtained by calculating the squared difference between the observed and
expected data, divided by the expected data in all possible categories, then
summing them. On its own, this value is difficult to interpret and therefore it is
given with a p-value. This is determined from a corresponding table.
The larger the difference between the observed and expected results, the larger
the Chi-squared value and the smaller the corresponding p-value. The p-value tells
you the strength of the evidence against the null hypothesis that the true difference
in the population is zero, i.e. there is no real difference between the groups.
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Equation 4.10: Chi-squared test 185
Therefore 2 = 53.09.
The p-value for this test, obtained from the table, is p < 0.001, i.e. there is
strong evidence against the null hypothesis of no effect of the vaccine on the
probability of contracting influenza.
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Likelihood ratio
Sensitivity
LR =
(1 Specificity)
Units
Fraction.
Explanation
The likelihood ratio uses sensitivity (refer to page 174) and specificity (refer to
page 172) to measure how much more probable it is that a test result would be
expected in a patient with a disease compared to the likelihood that the same test
result would occur in a patient without the disease. It is the probability of a
person who has the disease testing positive divided by the probability of a person
without the disease testing positive.
LR >1 indicates that the test result is associated with the disease.
LR < 1 indicates that the result is associated with absence of the disease.
The equation uses fractions not percentages.
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Equation 4.11: Likelihood ratio 187
1. Calculate the likelihood ratio for this new screening test for abdominal aortic
aneurysms.
Sensitivity
iii LR =
(1 Specificity)
= 86/(100 95)
= 17.2
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Standard error of mean
pffiffiffiffiffiffi
SEM = SD / (n)
Units
Nil.
Explanation
The standard error (SEM) of mean is an estimate of how close to the population
mean your sample mean is likely to be, i.e. a measure of the precision of your
sample mean as an estimate of the population mean. This is in contrast, and often
confused with, the standard deviation (refer to page 189), which measures the
amount of variability in the population and describes how individual observa-
tions within the sample differ from the population mean.
As the SEM depends on the standard deviation and sample size, as sample size
increases, the standard error of mean will decrease. The larger the sample size, the
smaller the standard error. By contrast, standard deviation will not be affected by
sample size.
pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
SD = variance
And
(x x)2
Variance = SD2 =
(n 1)
SD = standard deviation
= the sum of
x = individual observation
x = mean of all observations
n = number of observations in a sample
Units
Explanation
The standard deviation (SD) describes how spread out a set of observations are from
the mean (i.e. the variability or deviation of each observation from the mean value).
It is equal to the square root of the variance (the average of the squares of the
differences from the mean) in four easy steps.
(1) Calculate the mean for all the values (x ).
(2) For each individual observation (x), subtract the mean (x ) and square the
results (to make all positive). This is known as the squared deviation.
(3) Add all the observations together () and divide by the total number of
observations (n).
(4) Take the square root of the variance.
With the mean taken as the centre point, a range of one SD above (+) and below
() will include 68.3% of the values, 2 SD will include 95.4% of the values, and
3 SD will include 99.7% of the values.
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190 Section 4: Statistics
Standard deviation should only be used as a summary statistic when the data
have a normal distribution. To rapidly estimate whether this is the case, calculate
2SD above and below the mean, to see if the values are possible for the variable in
question.
NB: If you are sampling a small number of observations (n < 30), divide by n.
If you are sampling from a large number of observations (n >30), divide by
n 1. This is called Bessels correction and it corrects for bias in the estimation
of the population variance.
n=4
(x x)2
Variance = SD2 =
(n 1)
rffiffiffiffiffi
40
SD =
3
= 3.65 mg/dl
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Power
Power = 1
Units
Nil.
Explanation
The power of a statistical study measures the tests ability to reject the null
hypothesis when it is actually false (a Type II error) i.e. make the correct
decision. Given that the probability of a Type II error occurring is referred to as
the false negative rate (), and as power increases the chances of a Type II error
occurring decrease, power is therefore equal to 1 .
A Type II error would occur, for example, if a study concluded that two drugs
produced the same effect (i.e. the null hypothesis, there is no difference between
the drugs on average) when they actually produce different effects. Type II errors
frequently occur due to small sample sizes.
Power is calculated between 0 and 1, where 1 is the ideal power with no
chances of a Type II error occurring.
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Odds ratio
OR = odds ratio
a, b, c, d = as defined below
Units
Nil.
Explanation
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Equation 4.15: Odds ratio 193
1. It has been theorized that exposure to phenytoin increases your risk of developing
drug-induced lupus. Calculate the odds ratio for this association.
Drug-induced lupus
Phenytoin
Positive Negative
Yes 25 73
No 13 64
OR = (25/73)/(13/64) = 0.34/0.20
= 1.7
Exposure to phenytoin is associated with a higher odds of drug-induced lupus.
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Appendix 1: The International System
of Units
SI base units
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The International System of Units 195
SI-derived units
SI derived units are defined in terms of the seven base quantities using a system of
quantity equations. Twenty-two of these are named.
Expressed in Expressed in
terms of other terms of other SI
Derived quantity Name Symbol SI units base units
Plane angle Radian rad mm1 = 1
Solid angle Steradian sr m2m2 = 1
Frequency Hertz Hz s1
Force Newton N mkgs2
Pressure Pascal Pa N/m2 m1kgs2
Energy Joule J Nm m2kgs2
Power Watt W J/s m2kgs3
Electric charge Coulomb C sA
Electric potential Volt V W/A m2kgs3A1
difference
Electric Farad F C/V m2kg1s4A2
capacitance
Electric Ohm V/A m2kgs3A2
resistance
Electric Siemens S A/V m2kg1s3A2
conductance
Magnetic flux Weber Wb Vs m2kgs2A1
Magnetic flux Tesla T Wb/m2 kgs2A1
density
Inductance Henry H Wb/A m2kgs2A2
Celsius Degree
C K
temperature Celsius
Luminous flux Lumen lm cdsr m2m2cd = Cd
Illuminance Lux lx lm/m2 m2m4cd =
m2Cd
Radioactivity Becquerel Bq s 1
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Appendix 2: Units of measurement
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Index
Terms from Chapter titles in the list of Contents are not included
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198 Index
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Index 199
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